THU410 Retrospective Review Of Adults Patients With Suspected Or Confirmed Hypophosphatasia At The Penn Bone Center

Abstract

Abstract Disclosure: R. Tran: None. C. Hvisdas: None. M. Riordan: None. L. Novotny: None. S. Kallish: None. K. Patel: None. M. Al Mukaddam: None. Abstract: Hypophosphatasia (HPP) is a rare inherited genetic disorder that affects the mineralization of bones and teeth. HPP is the result of a pathogenic variant involving the tissue nonspecific alkaline phosphatase (ALPL) gene. The clinical presentations of HPP greatly vary from serious perinatal manifestations (respiratory failure, seizures, and death) to mild manifestations in adulthood. In adults, hallmark signs and symptoms include early loss of primary or secondary teeth, osteoporosis, osteomalacia, recurring metatarsal stress fractures, and abnormal laboratory values, such as low alkaline phosphatase (ALP), elevated phosphoethanolamine, and elevated vitamin B6.The treatment and follow up of adults with HPP are not clearly described. This retrospective study characterizes 43 patients referred to the Penn Bone Center for suspected HPP. Twelve of the 43 patients had a confirmed HPP diagnosis based on both clinical presentations and evidence of variant in the ALPL gene. The twelve patients consisted of both female and male adults between the ages of 24 to 74. In addition, the patients had abnormal ALP levels, ranging between less than 5 to 38 units per liter (normal range: 38 to 126 U/L). Six of these patients had previous or current use of asfotase alfa with variable treatment response. Two patients decided to stop treatment due to lack of clinical benefit or worsening of symptoms while on asfotase alfa therapy. Biochemical and bone mineral density follow-up while on therapy has not been shown to be helpful in monitoring treatment response. Asfotase alfa is a subcutaneously administered synthetic human alkaline phosphatase that was approved by the Federal Drug Administration (FDA) in 2015 for treatment of perinatal/infantile- and juvenile-onset hypophosphatasia. However, the efficacy of treatment in adults remain unclear at this time. Further research is required to better define the natural progression of mild or adult-onset hypophosphatasia and the patients who would benefit from enzyme therapy. Presentation: Thursday, June 15, 2023